Lantern Pharma & Starlight Therapeutics Present LP-184 (STAR-001) Phase 1b Trial Design and Preclinical Data in Glioblastoma at Society for Neuro-Oncology (SNO) 2024 Highlighting Novel Synthetic Lethality

On November 26, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence company transforming oncology drug development, and its wholly-owned subsidiary Starlight Therapeutics, focused exclusively on CNS and brain cancers, reported the presentation of new preclinical data and Phase 1b trial design for LP-184 (to be developed as STAR-001 for CNS indications) in glioblastoma at the Society for Neuro-Oncology (SNO) 2024 Annual Meeting in Houston, Texas (Press release, Lantern Pharma, NOV 26, 2024, View Source [SID1234648673]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster presentation highlighted LP-184’s unique mechanism of action, brain penetrance properties, and potential enhanced therapeutic effect when combined with spironolactone in glioblastoma multiforme (GBM). LP-184 is currently under investigation in a Phase 1a dose-escalation safety study (NCT05933265) in adult patients with advanced solid tumors including GBM.

"The data and trial design presented at SNO2024 further validate and progress LP-184’s potential as a promising new treatment option for glioblastoma patients," said Panna Sharma, President and CEO of Lantern Pharma. "Through our subsidiary Starlight Therapeutics, we are positioned to advance LP-184 as STAR-001 specifically for brain cancers and CNS indications, where treatment options are limited and often ineffective. The combination with spironolactone represents an innovative approach, which has been developed with the aid of our AI platform RADR, to potentially enhance therapeutic response in this devastating disease."

The key highlights from the poster presented by Dr. Schreck from Johns Hopkins Medicine and Dr. Kulkarni from Lantern Pharma at SNO2024 include:

LP-184 shows favorable brain penetrance with a brain tumor/plasma concentration ratio of 0.2 compared to 0.1 for the existing standard of care, temzolomide.
Preclinical studies show spironolactone increases GBM cell sensitivity to LP-184 up to 6-fold through ERCC3 degradation – which induces NERD (nucleotide excision repair deficiency) making the cancer cells both more sensitive to LP-184/STAR-001 and largely unable to repair themselves after exposure to the drug-candidate.
Multiple time point and dose level experiments show that GBM cells treated with spironolactone showed significant depletion of ERCC3 – including at 25μM of spironolactone which showed up-to 95% depletion of ERCC3 by 24h.
LP-184 is effective in temozolomide-resistant GBM models and is agnostic to MGMT methylation status.
PTGR1 expression analysis from GTEX normal brain and TCGA GBM highlights that PTGR1 levels are higher in brain tumor tissue (median 5.15) as compared to normal brain tissue (median 3.95).
ERCC3-dependent TC-NER activity was identified as a determinant of LP-184 synthetic lethality predicting that LP-184’s therapeutic potential will be enhanced in patients with intrinsic or spironolactone-induced NER deficient tumors.
Phase 1b trial being considered will evaluate LP-184 as both monotherapy and in combination with spironolactone using Simon’s 2-stage optimal design in patients with IDH wild type GBM at first progression.
Following determination of the Maximum Tolerated Dose and/or Recommended Phase 2 Dose from the ongoing Phase 1a study, Starlight Therapeutics plans to initiate a Phase 1b trial evaluating LP-184/STAR-001 in two cohorts of recurrent GBM patients: one arm which anticipates administration of STAR-001 as monotherapy and the other arm which anticipates administration of STAR-001 in combination with spironolactone (200 mg daily).

The trial, as currently anticipated and designed, will assess safety, pharmacokinetics, and objective response using RANO 2.0 criteria. Additionally, the study will evaluate biomarkers including PTGR1 expression, ERCC3 levels, and DNA damage markers to help identify patients most likely to respond to treatment. Lantern has previously reported on achieving significant development milestones in the creation of a molecular diagnostic using quantitative PCR to assess PTGR1 levels from clinical patient samples.

LP-184 (to be developed as STAR-001 for CNS indications) is a fully synthetic small molecule that belongs to the acylfulvene class of alkylating agents. It induces DNA double-strand breaks and has shown promise across a range of solid tumors, including in preclinical GBM models. LP-184 is activated by PTGR1, which is over-expressed in approximately 80% of recurrent GBM tumors. The FDA has granted LP-184 both Orphan Drug and Fast Track designations for the treatment of malignant gliomas / glioblastoma.

Summit Therapeutics to Present at Upcoming Investor Conferences

On November 26, 2024 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported that it will participate in and present at the 7th Annual Evercore HealthCONx Conference and Citi’s 2024 Global Healthcare Conference, both being held in Miami. Our management team will participate in fireside chats surrounding the development of our innovative investigational bispecific antibody, ivonescimab, at the Evercore HealthCONx Conference on Tuesday December 3, 2024 at 8:45am ET, and the Citi Global Healthcare Conference on Wednesday December 4, 2024 at 8:45am ET (Press release, Summit Therapeutics, NOV 26, 2024, View Source [SID1234648672]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Presentations from both conferences will be available live from our website: www.smmttx.com. An archived version of both presentations will be available on our website following the presentation.

SystImmune, Inc. Announces Upcoming Presentation at the 2024 American Society of Hematology (ASH) Annual Meeting

On November 26, 2024 SystImmune, Inc. (SystImmune), a clinical-stage biotechnology company, reported an upcoming poster presentation on BL-M11D1, an antibody drug conjugate (ADC) targeting CD33 at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being hosted December 7 – 10th, 2024 in San Diego, CA (Press release, SystImmune, NOV 26, 2024, View Source [SID1234648670]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

BL-M11D1 is a potentially best-in-class ADC against CD33, a clinically validated target in AML and leverages the same linker payload as our lead program, BL-B01D1. Pre-clinical data disclosed earlier showed BL-M11D1 exhibited strong anti-tumor activity in CD33 expressing AML xenograft models and cell lines. At ASH (Free ASH Whitepaper) we will present initial safety and efficacy data from the dose escalation portion of the study in relapsed/refractory AML patients. "These data support our conviction that BL-M11D1 has a potentially differentiated safety profile and can offer an important therapeutic option for patients with relapsed/refractory AML" said Jonathan Cheng, M.D., CMO of SystImmune. "The clinical data presented here and the recent approval of the BL-M11D1 US IND positions us to rapidly expand the program not only as a monotherapy but also in combination with other agents and improve outcomes for AML patients globally."

Details on for the ASH (Free ASH Whitepaper) 2024 poster presentations are as follows:
BL-M11D1, a Novel CD33 Antibody-Drug Conjugate (ADC), in Patients with Relapsed/ Refractory Acute Myeloid Leukemia: Initial Results from First-in-Human Phase 1 Study
Speaker: Lin Song (Tianjin, China)
Publication Number: 4260
Session Name: 616: Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster III
Session Date & Time: Monday, December 9th, 2024, 6:00 PM-8:00 PM PST
Location: San Diego Convention Center, Halls G-H

The abstract is available online and can be accessed via the conference websites at ASH (Free ASH Whitepaper) Annual Meeting Abstracts.

About BL-M11D1
The company is developing BL-M11D1, an ADC comprising a monoclonal antibody component binding CD33 and a linker-payload component that is composed of a topoisomerase I inhibitor payload and a stable enzyme-cleavable linker. BL-M11D1 works by triggering antibody-dependent cellular cytotoxicity (ADCC) when it binds to CD33 on cancer cells. In addition, the binding to CD33 causes its internalization followed by the release of the payload, which then kills the tumor cell.

Menarini Group Presents New and Expanded Data at the 2024 San Antonio Breast Cancer Symposium Reinforcing the Role of ORSERDU® (Elacestrant) for Patients with ER+, HER2- Advanced or Metastatic Breast Cancer (mBC)

On November 26, 2024 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group, focused on bringing transformational oncology treatments to cancer patients, reported that it will present new and expanded data on ORSERDU (elacestrant) at the upcoming 2024 San Antonio Breast Cancer Symposium (SABCS), December 10-13, 2024 (Press release, Menarini, NOV 26, 2024, View Source;advanced-or-metastatic-breast-cancer-mbc-302316326.html [SID1234648669]). Of note, the company will bring real-world progression-free survival (rwPFS) results of ORSERDU in adult patients with ER+/HER2-, advanced or metastatic breast cancer (mBC). Additionally, the company will present updated efficacy results of elacestrant plus abemaciclib, along with a pooled safety analysis from phase 1b/2 of both the ELECTRA and ELEVATE trials.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ORSERDU Real-World Progression-Free Survival Data

ORSERDU is the first and only oral estrogen receptor antagonist (SERD) approved to target ESR1-mutated tumors, which occur in up to 50% of ER+, HER2- advanced or mBC tumors, as a result of prior exposure to endocrine therapy (ET) in the metastatic setting. Since its approval by the U.S. Food & Drug Administration (FDA) in January 2023, sufficient time has passed to be able to characterize the real-world use of ORSERDU in the current mBC treatment landscape.

Results to be reported at SABCS 2024 show the efficacy of ORSERDU in the real-world setting in patients with ER+/HER2- advanced or mBC. The overall population analysis demonstrated median rwPFS of 6.8 months. Median rwPFS for patients with 1-2 lines of prior ET in mBC was 8 months. The rwPFS observed is consistent across the subgroups in the analysis. Updated results and additional information from other patient subgroups will be presented at the congress.

The full abstract (SESS-1876) can be viewed here (page 1748).

"These exciting data show clinically meaningful real-world progression-free survival with ORSERDU monotherapy," said Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center. "As a practicing physician, these results underscore the need to test patients’ tumors for the ESR1 mutation at each disease progression using liquid biopsy, so that we can appropriately tailor their treatment and optimize their care."

Elacestrant Plus Abemaciclib Combination Study

Both the ELEVATE and ELECTRA phase 1b/2 studies were designed with the objective to evaluate patient outcomes through combination treatment options, by overcoming a tumor’s resistance to ET.

Results to be reported at SABCS 2024 include updated efficacy results from the ELECTRA study which demonstrate favorable progression-free survival (PFS) data. In all efficacy-evaluable patients, median progression-free survival (mPFS) was 8.6 months. In patients with an ESR1 mutation, mPFS was 8.7 months. In patients without an ESR1 mutation, mPFS was 7.2 months.

Additionally, a pooled safety analysis of patients from ELECTRA and ELEVATE show a manageable and predictable safety profile in patients with ER+/HER2- mBC that is treated with elacestrant plus abemaciclib, and who previously received one or more lines of prior therapy. Safety was evaluated in all patients who received this combination and was consistent with the known safety profiles of both compounds. The most common all-grade adverse events (AEs) (≥20%) were diarrhea, nausea, neutropenia, vomiting, fatigue, anemia and decreased appetite. No Grade 4 AEs were observed.

The full abstract (SESS-1910) can be viewed here (page 3330).

"These updated results on the combination of elacestrant plus abemaciclib continue to show encouraging progression-free survival data, and a favorable safety profile, without any new toxicity signals when using these agents in combination," said Hope S. Rugo, MD, Professor of Medicine and Winterhof Family Endowed Professor in Breast Cancer, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco. "Elacestrant continues to show potential to become an endocrine therapy backbone for combination regimens in metastatic breast cancer, and we are excited to explore this treatment combination further as these trials move forward."

"It is exciting to see these progression-free survival outcomes in a real-world setting, which shows ORSERDU brings a meaningful benefit for oncologists to offer their patients," said Elcin Barker Ergun, CEO of the Menarini Group. "We are committed to advancing our robust clinical research program on elacestrant and unlocking its full potential, both in monotherapy and combination treatment settings, with the goal of bringing ORSERDU to new patient populations which may benefit."

Menarini Stemline will also share results of other relevant data from the Phase 3 EMERALD trial, as well as several trials in progress.

Complete List of Menarini Stemline Abstracts:

Title: Elacestrant real-world progression-free survival (rwPFS) of adult patients with ER+/HER2-, advanced breast cancer: a retrospective analysis using insurance claims in the United States
Poster Number: P3-10-08
Date & Time: Thursday, December 12, 12-2 PM CST
Location: TBC
Presenting Author: Elyse Swallow

Title: Elacestrant plus abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC)
Poster Number: PS7-07
Date & Time: Thursday, December 12, 7-8:30 AM CST
Location: TBC
Presenting Author: Hope Rugo

Title: Elacestrant combination in patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (mBC): Update from ELEVATE, a phase 1b/2, open-label, umbrella study
Poster Number: PS7-06
Date & Time: Thursday, December 12, 7-8:30 AM CST
Location: TBC
Presenting Author: Hope Rugo

Title: Elacestrant vs SOC in ER+, HER2- advanced or metastatic breast cancer (mBC) with ESR1-mutated tumors: ESR1 allelic frequencies and clinical activity from the phase 3 EMERALD trial
Poster Number: P1-01-25
Date & Time: Wednesday, December 11, 12-2 PM CST
Location: TBC
Presenting Author: Aditya Bardia

Title: ELEGANT: Elacestrant versus standard endocrine therapy in women and men with node-positive, estrogen receptor-positive, HER2-negative, early breast cancer with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study
Poster Number: P2-08-21
Date & Time: Wednesday, December 11, 5:30-7:30 PM CST
Location: TBC
Presenting Author: Aditya Bardia

Title: ADELA: A randomized, phase 3, double-blind, placebo-controlled trial of elacestrant plus everolimus versus elacestrant in ER+/HER2-advanced breast cancer (aBC) patients with ESR1-mutated tumors progressing on endocrine therapy (ET) plus CDK4/6i
Poster Number: P2-10-21
Date & Time: Wednesday, December 11, 5:30-7:30 PM CST
Location: TBC
Presenting Author: Antonio Llombart-Cussac

Title: ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study
Poster Number: P2-08-20
Date & Time: Wednesday, December 11, 5:30-7:30 PM CST
Location: TBC
Presenting Author: Virginia Kaklamani

About The Elacestrant Clinical Development Program

Elacestrant is also being investigated in several company-sponsored clinical trials in metastatic breast cancer, alone or in combination with other therapies. EMERALD (NCT03778931) is a randomized Phase 3 trial, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. ELEVATE (NCT05563220) is a phase 1b/2 clinical trial evaluating the safety and efficacy of elacestrant combined with alpelisib, everolimus, capivasertib, palbociclib, ribociclib or abemaciclib. ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- breast cancer. The phase 2 portion evaluates this treatment regimen in patients with brain metastases. ELCIN (NCT05596409) is a phase 2 trial evaluating the efficacy of elacestrant in patients with ER+, HER2- advanced/metastatic breast cancer who received one or two prior hormonal therapies and no prior CDK4/6 inhibitors in the metastatic setting. ADELA (NCT06382948) is a phase 3 randomized, double-blinded trial evaluating elacestrant in combination with everolimus in patients with ER+, HER2- mBC with ESR1-mut tumors. ELEGANT (NCT06492616) is a phase 3 study evaluating elacestrant versus standard endocrine therapy in women and men with node-positive, estrogen receptor-positive, HER2-negative, early breast cancer with high risk of recurrence. Elacestrant is also being evaluated in additional investigator-led trials, in trials conducted in collaboration with other companies, in metastatic breast cancer as well as in early disease.

About ORSERDU (elacestrant)

U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information for the U.S. can be found at www.orserdu.com.

Important Safety Information

Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (≥10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.

Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).

The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Verastem Oncology to Present at the 7th Annual Evercore ISI HealthCONx Conference

On November 26, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that its management team will participate in a fireside chat at the 7th Annual Evercore ISI HealthCONx Conference on Tuesday, December 3rd at 11:15 am EST (Press release, Verastem, NOV 26, 2024, https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-present-7th-annual-evercore-isi-healthconx [SID1234648668]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A live webcast of the fireside chat can be accessed under "Events & Presentations" in the Investors & Media section of the company’s website at www.verastem.com. A replay of the webcast will be archived on the website for approximately 90 days following the presentation.